Methods and devices for three-stage ventricular therapy

ABSTRACT

Methods and apparatus for a three-stage ventricular cardioversion and defibrillation therapy that treats ventricular tachycardia and fibrillation at low energy levels. An implantable therapy generator adapted to generate and selectively deliver a three-stage ventricular therapy and at least two leads operably each having at least one electrode adapted to be positioned proximate the ventricle of the patient. The device is programmed to deliver a three-stage therapy via both a far-field configuration and a near-field configuration of the electrodes upon detection of a ventricular arrhythmia. The three-stage therapy includes a first stage for unpinning of one or more singularities associated with the ventricular arrhythmia, a second stage for anti-repinning of the one or more singularities, both of which are delivered via the far-field configuration of the electrodes, and a third stage for extinguishing of the one or more singularities associated delivered via the near-field configuration of the electrodes.

RELATED APPLICATIONS

The present application is a continuation-in-part of U.S. patentapplication Ser. No. 12/776,196, now U.S. Pat. No. 8,560,066, filed May7, 2010 which is a continuation-in-part of U.S. patent application Ser.No. 12/333,257, now U.S. Pat. No. 8,509,889, filed Dec. 11, 2008, whichclaims the benefit of U.S. Provisional Application No. 61/012,861, filedDec. 11, 2007, each of which is incorporated herein by reference.

FIELD OF THE INVENTION

The present disclosure relates generally to the treatment of ventriculararrhythmias. More particularly, the present disclosure relates todevices and methods of using low-energy electrical stimuli from animplantable device that delivers a three-stage ventricular cardioversionand defibrillation therapy to destabilize and extinguish reentrymechanisms that maintain ventricular tachycardia and ventricularfibrillation.

BACKGROUND OF THE INVENTION

It is well-known that rotating waves of electrical activity are a factorin potentially dangerous cardiac arrhythmias such as ventriculartachycardia and ventricular fibrillations (VT/VF). The rotating waves,or reentries, that are responsible for ventricular tachycardia eventsare classified into two categories: 1) functional reentries, whichinvolve freely rotating waves; and 2) anatomical reentries, where a waverotates around an obstacle such as a blood vessel or piece of ischemictissue. The latter are referred to as being ‘pinned’ by the obstacle.Traditional defibrillation is not a preferred way of dealing with suchrotating waves because defibrillation resets electrical activityeverywhere in the heart and uses high voltage shocks, which haveundesirable side effects.

One common method of attempting to terminate these rotating waves orreentries is anti-tachycardia pacing (ATP). ATP has a high rate ofsuccess in dealing with functional reentries, but is not as effectiveagainst anatomical reentries. Generally, if ATP is not effective, adefibrillation shock of large amplitude is applied directly to cardiacmuscle.

Such high voltage, high energy shocks may be delivered by a standardexternal defibrillator with the patient sedated during delivery of adefibrillation shock. However, in order to provide an external shockthat can effectively terminate arrhythmias with electrodes placedexternally on the body, such systems must provide higher energy shocksthan would be required by implantable devices. In addition, externallyapplied shocks necessarily recruit more of the skeletal musculatureresulting in potentially more pain and discomfort to the patient.

Another method of treatment for patients experiencing ventriculartachycardia (VT) or ventricular fibrillation (VF) is the implantablecardioverter defibrillator (“ICD”). However, the energy level needed forsuccessful cardioversion can also exceed the pain threshold. Endocardialcardioversion shock energies greater than 0.1 J are perceived to beuncomfortable (Ladwig, K. H., Marten-Mittag, B., Lehmann, G., Gundel,H., Simon, H., Alt, E., Absence of an Impact of Emotional Distress onthe Perception of Intracardiac Shock Discharges, International Journalof Behavioral Medicine, 2003, 10(1): 56-65), and patients can fail todistinguish energy levels higher than this and find them equallypainful. The pain threshold depends on many factors, including autonomictone, presence of drugs, location of electrodes and shock waveforms.Moreover, pain thresholds can be different from patient to patient.Further, as compared to external defibrillators, ICD's present otherchallenges, including a limited energy source.

Many systems have sought to lower the energy level required foreffective atrial fibrillation. A number of systems, such as, forexample, U.S. Pat. No. 5,282,836 to Kreyenhagen et al., U.S. Pat. No.5,797,967 to KenKnight, U.S. Pat. Nos. 6,081,746, 6,085,116 and6,292,691 to Pendekanti et al., and U.S. Pat. Nos. 6,556,862 and6,587,720 to Hsu et al. disclose application of atrial pacing pulses inorder to lower the energy level necessary for atrial defibrillationshocks. The energy delivered by pacing pulses is relatively nominal incomparison to defibrillation shocks. U.S. Pat. No. 5,620,468 to Mongeonet al. discloses applying cycles of low energy pulse bursts to theatrium to terminate atrial arrhythmias. U.S. Pat. No. 5,840,079 toWarman et al. discloses applying low-rate ventricular pacing beforedelivering atrial defibrillation pulses. U.S. Pat. No. 5,813,999 toAyers et al. discloses the use of biphasic shocks for atrialdefibrillation. U.S. Pat. Nos. 6,233,483 and 6,763,266 to Krolldiscloses the use of multi-step defibrillation waveform, while U.S. Pat.No. 6,327,500 to Cooper et al. discloses delivering two reduced-energy,sequential defibrillation pulses instead of one larger energydefibrillation pulse.

However, reduced-energy AF treatments do not necessarily translate wellto VT or VF treatments in part due to the physiological differences inthe causes of AF vs. VF, but also in part due to the criticality of VTand VF.

Consequently, there remains a need for improved VT and VF treatmentmethods and devices enabling successful electrical treatment withoutexceeding the pain threshold of a patient.

SUMMARY OF THE INVENTION

Embodiments of methods and apparatus in accordance with the presentdisclosure provide for a three-stage ventricular cardioversion anddefibrillation therapy to treat ventricular tachycardias (VTs) andventricular fibrillation (VF) within pain tolerance thresholds of apatient. A VT/VF therapy in accordance with various embodiments includesan implantable therapy generator adapted to generate and selectivelydeliver a three-stage ventricular therapy and at least two leadsoperably connected to the implantable therapy generator, each leadhaving at least one electrode adapted to be positioned proximate theventricle of a heart of the patient. The ventricular arrhythmiatreatment device is programmed with a set of therapy parameters fordelivering a three-stage cardioversion or defibrillation therapy to apatient via both a far-field configuration and a near-fieldconfiguration of the electrodes upon detection of a ventriculararrhythmia by the ventricular arrhythmia treatment device.

In an embodiment, the three-stage therapy comprises a three-stageventricular therapy that includes a first stage for unpinning of one ormore singularities associated with a ventricular arrhythmia, a secondstage for anti-repinning of the one or more singularities associatedwith the ventricular arrhythmia, and a third stage for extinguishing ofthe one or more singularities associated with the ventriculararrhythmia. In various embodiments, the first stage has two to tenbiphasic far field ventricular cardioversion/defibrillation pulses oftwo volts to 100 volts delivered within one to two VT/VF cycle lengths(CLs). The second stage comprises six to ten far field pulses of one tofive times the ventricular shock excitation threshold, generally 0.5 to20 volts, with a pulse coupling interval of between 70-100% of VT/VFcycle length. The third stage comprises eight to twelve near fieldpulses at a voltage of two to four times the strength of the diastolicventricular pacing threshold, with a pulse coupling interval of between70-100% of the VT/VF cycle length. The three-stage ventricular therapyis delivered in response to detection of the ventricular arrhythmia,with each stage having an inter-stage delay of 50 to 800 milliseconds,and in some embodiments, without confirmation of conversion of theventricular arrhythmia until after delivery of the third stage.

In various embodiments, a ventricular arrhythmia treatment apparatusincludes at least one electrode adapted to be implanted proximate aventricle of a heart of a patient to deliver far field pulses and atleast one electrode adapted to implanted proximate a ventricle of theheart of the patient to deliver near field pulses and sense cardiacsignals. An implantable therapy generator is operably connected to theelectrodes and includes a battery system operably coupled and providingpower to sensing circuitry, detection circuitry, control circuitry andtherapy circuitry of the implantable therapy generator. The sensingcircuitry senses cardiac signals representative of ventricular activity.The detection circuitry evaluates the cardiac signals representative ofventricular activity to determine a ventricular cycle length and detecta ventricular arrhythmia. The control circuitry, in response to theventricular arrhythmia, controls generation and selective delivery of athree-stage ventricular therapy to the electrodes with each stage havingan inter-stage delay of between 50 to 800 milliseconds. The therapycircuitry is operably connected to the electrodes and the controlcircuitry and includes at least one first stage charge storage circuitselectively coupled to the at least one far field electrode thatselectively stores energy for a first stage of the three-stageventricular therapy, at least one second stage charge storage circuitselectively coupled to the at least one far field electrode thatselectively stores a second stage of the three-stage ventriculartherapy, and at least one third stage charge storage circuit selectivelycoupled to the near field electrode that selectively stores a thirdstage of the three-stage ventricular cardioversion therapy.

The methods and devices of the present disclosure can exploit a virtualelectrode polarization (“VEP”) enabling successful treatment of VT or VFwith an implantable system without exceeding the pain threshold of apatient. This is enabled by far-field excitation of multiple areas oftissue at once, rather than just one small area near a pacing electrode,which can be more effective for both VT and VF. The methods can differfrom conventional defibrillation therapy, which typically uses only onehigh-energy (about five to about forty-one joules) monophasic orbiphasic shock or two sequential monophasic shocks from two differentvectors of far-field electrical stimuli.

The methods and devices of embodiments of the present disclosure canutilize a low-voltage phased unpinning far-field therapy together withnear-field therapy that forms the three-stage ventricular cardioversiontherapy to destabilize or terminate the core of a mother rotor, whichanchors to a myocardial heterogeneities such as scar from myocardialinfarction, coronary arteries or other fibrotic areas. A significantreduction in the energy required to convert a ventricular arrhythmia canbe obtained with this unpinning, anti-repinning and then extinguishingtechnique compared with conventional high-energy defibrillation, thusenabling successful cardioversion without exceeding the pain thresholdof a patient.

Applying far-field low energy electric field stimulation in anappropriate range of time- and frequency-domains can interrupt andterminate the reentrant circuit by selectively exciting the excitablegap near the core of reentry. By stimulating the excitable gap near thecore of the circuit, the reentry can be disrupted and terminated. Thereentrant circuit is anchored at a functionally or anatomicallyheterogeneous region, which constitutes the core of reentry. Areas nearthe heterogeneous regions (including the region of the core of reentry)will experience greater polarization in response to an applied electricfield compared with the surrounding, more homogeneous tissue. Thus, theregion near the core of reentry can be preferentially excited with verysmall electric fields to destabilize or terminate anchored reentrantcircuits. Once destabilized, subsequent shocks can more easily terminatethe arrhythmia and restore normal sinus rhythm.

Virtual electrode excitation can be used at local resistiveheterogeneities to depolarize a critical part of the reentry pathway orexcitable gap near the core of reentry. Various pulse protocols for athree-stage ventricular cardioversion/defibrillation therapy toterminate ventricular arrhythmias in accordance with aspects of thepresent invention are contemplated. In one aspect, the reentry is eitherterminated directly or destabilized by far-field pulses delivered in afirst and second stage and then terminated by additional stimuli bynear-field pulses delivered in a third stage of the three-stage therapy.The low energy stimulation can be below the pain threshold and, thus,may cause no anxiety and uncomfortable side effects to the patient. Inanother aspect, a phased unpinning far-field therapy can be delivered inresponse to a detected ventricular arrhythmia, with post treatmentpacing administered as a follow-up therapy to the phased unpinningfar-field therapy.

To further optimize this low energy method of termination, multipleelectric field configurations can be used to optimally excite theexcitable gap near the core of reentry and disrupt the reentrantcircuit. These field configurations can be achieved by placing severaldefibrillation leads/electrodes into the right ventricle, coronarysinus, and the left ventricular veins. Electric fields can be deliveredbetween any two or more of these electrodes as well as between one ofthese electrodes and the device itself (hot can configuration). Inanother aspect, segmented electrodes with the ability to selectivelyenergize one or more of the electrode segments can be used. Modulationof the electric field vector can then be used to achieve maximumcoverage of the heart.

In another aspect of the present invention, the morphology of anelectrogram of an arrhythmia can be documented, stored, and compared topreviously stored morphologies. Anatomic location(s) of the reentrycircuit(s) may be determined by the specific anatomy and physiologicalremodeling of the atria, which are unique for each patient. Theembodiment takes advantage of the observation that several morphologiesof ventricular arrhythmias tend to occur with higher frequency thanothers. Optimization of electric field configuration and pulse sequenceof the therapy may be conducted separately for each electrogrammorphology and stored in memory for future arrhythmia terminations. Whenan arrhythmia is detected, it will be determined whether the morphologyof the electrogram of an arrhythmia is known. If it is, the optimizedtherapy stored in memory may be applied to convert that arrhythmia.

In another aspect of the present invention, an implantable cardiactherapy device for treating a in need of defibrillation includes one ormore sensors comprising one or more implanted electrodes positioned indifferent locations for generating electrogram signals, one or morepacing implanted electrodes positioned in different locations fornear-field pacing of different sites, one or more implanteddefibrillation electrodes positioned in different locations forfar-field delivery of electrical current, and an implantable or externaldevice which can be capable to deliver a train of pulses.

In one exemplary embodiment, the implantable device is implanted justunder the left clavicle. This location places the device in approximatealignment with the longitudinal anatomical axis of the heart (an axisthrough the center of the heart that intersects the apex and theinter-ventricular septum). When the electrodes are implanted in thismanner, the arrangement of the device and electrodes is similar inconfiguration to the top of an umbrella: the device constituting theferrule of an umbrella, and the electrodes constituting the tines of theumbrella. The electrodes of the device are energized in sequential orderto achieve electrical fields of stimulation that is similar to“stimulating” the triangles of umbrella fabric, one after the other, ineither a clockwise or counter-clockwise manner or in a custom sequence.Leads may be active or passive fixation.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be more completely understood in consideration of thefollowing detailed description of various embodiments of the inventionin connection with the accompanying drawings, in which:

FIG. 1A depicts a schematic anterior view of a human heart andanatomical locations of implantable defibrillation leads, with a leadplaced in the right ventricle (RV), and an epicardial patch (LVP) placedover the left ventricle;

FIG. 1B depicts a schematic posterior view of a human heart andanatomical locations of implantable defibrillation leads with a leadplaced in the coronary sinus (CS) and the left ventricular vein (LVC);

FIGS. 2A-E depict multiple simplified schematic anterior and posteriorviews of a human heart, depicting various anatomical locations ofimplantable defibrillation leads and electrodes, with arrows indicatingelectric field vectors between leads and electrodes;

FIG. 3 depicts an embodiment of a three-stage ventricular therapy,according to an embodiment of the claimed invention;

FIG. 4 depicts an embodiment of a stimulation waveform of thethree-stage therapy of FIG. 3;

FIG. 5 depicts an embodiment of a first, unpinning stage of the waveformof FIG. 4;

FIG. 6 depicts an embodiment of a second, anti-repinning stage of thewaveform of FIG. 4;

FIG. 7 depicts an embodiment of a third, extinguishing stage of thewaveform of FIG. 4;

FIG. 8 depicts another embodiment of applying stimulation in the form ofa three-stage ventricular therapy;

FIG. 9 depicts an embodiment of a stimulation waveform of thethree-stage ventricular therapy of FIG. 8;

FIG. 10 depicts yet another embodiment of applying stimulation in theform of a three-stage ventricular therapy;

FIG. 11 depicts yet another embodiment of a stimulation waveform of thethree-stage therapy of FIG. 10;

FIGS. 12A and 12B are block diagrams depicting of an embodiment of athree-stage ventricular therapy device, and the therapy circuitrythereof, respectively;

FIGS. 13A-13H depict various portions of the therapy circuitry of thedevice of FIGS. 12A and 12B, in greater detail, according to variousembodiments; and

FIG. 14 depicts a sample comparison of voltage and energy ventriculardefibrillation thresholds of a single-biphasic shock and the three-stagetherapy of FIG. 4.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail. It should be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the intention is tocover all modifications, equivalents, and alternatives falling withinthe spirit and scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION

Embodiments of the present disclosure are based on a low-voltage phasedunpinning far-field therapy together with near-field therapy that formsthe three-stage ventricular cardioversion and defibrillation therapy fordestabilizing and subsequently terminating anatomical reentranttachyarrhythmias. A significant reduction in the energy required toconvert a ventricular arrhythmia can be obtained with this unpinning,anti-repinning and then extinguishing technique compared withconventional high-energy defibrillation. Furthermore, the low-energy,ventricular therapy enables successful cardioversion without exceedingthe pain threshold of a patient. With respect to pain and pain-relatedsubject matter described hereinafter, it will be understood that suchdescription generally relates to cardioversion of ventriculartachycardia (VT), rather than conversion of ventricular fibrillation(VF). Further, it will be understood the term “cardioversion” refersspecifically to cardioversion of a VT, and that defibrillation refersspecifically to defibrillation of a VF, though in some instances,cardioversion may in a broad sense be used to describe termination of aventricular arrhythmia that may comprise VT or VF.

The anatomical structure of cardiac tissue can be inherentlyheterogeneous. These syncytial heterogeneities of even modestproportions can represent a significant mechanism contributing to thefar-field excitation process. Fishler, M. G., Vepa K., SpatiotemporalEffects of Syncytial Heterogeneities on Cardiac Far-field Excitationsduring Monophasic and Biphasic Shocks, Journal of CardiovascularElectrophysiology, 1998, 9(12): 1310-24, which is incorporated herein byreference.

For purposes of the present application, the term “near-field,” canrelate to effects that are in close proximity to stimulatingelectrode(s), i.e., distances are restricted by several space constants(lambda) of cardiac tissue, which is typically up to severalmillimeters. Near-field effects can be strongly dependent upon distancefrom the electrodes. The term “far-field,” on the other hand, can relateto effects that are generally independent or less dependent upondistance from the electrodes. They can occur at distances that are muchgreater than the space constant (lambda).

Applying far-field low energy electric field stimulation in a range oftime- and frequency-domains can interrupt and terminate the reentrantcircuit by selectively exciting the excitable gap near the core ofreentry. High frequency far-field electric stimulation has significantlyhigher defibrillation success compared to near-field ATP. The reentrantcircuit can be anchored at a functionally or anatomically heterogeneousregion, which constitutes the core of reentry. The virtual electrodetheory of myocardial excitation by electric field predicts that areasnear the core will experience greater polarization in response to anapplied electric field compared with the surrounding, more homogeneoustissue. Various shock protocols to terminate ventricular arrhythmias arecontemplated. Thus, in one aspect, the region near the core of reentrycan be preferentially excited with very small electric fields todestabilize or terminate anchored reentrant circuits. Once destabilized,subsequent shocks can more easily drive the rotors away to the boundaryof atrial tissue and restore normal sinus rhythm.

In traditional high-voltage defibrillation therapy, a truncatedexponential biphasic waveform has a lower defibrillation energy ascompared to monophasic shocks. However, in the case of phased unpinningfar-field therapy (“PUFFT”), the use of multiple monophasic versusmultiple biphasic waveforms was recently found to be more effective interminating ventricular tachycardias in a rabbit model. This differencewas thought to exist because optimal biphasic defibrillation waveformsmay not produce VEPs because of an asymmetric effect of phase reversalon membrane polarization. Efimov, I. R., Cheng, Y., Van Wagoner, D. R.,Mazgalev, T., Tchou, P. J., Virtual Electrode-Induced Phase Singularity:A Basic Mechanism of Defibrillation Failure, Circulation Research, 1998,82(8): 918-25, which is incorporated herein by reference. VEP isdiscussed further in Efimov, I. R., Cheng, Y. N., Biermann, M., VanWagoner, D. R., Mazgalev, T. N., Tchou, P. J., Transmembrane VoltageChanges Produced by Real and Virtual Electrodes During MonophasicDefibrillation Shock Delivered by an Implantable Electrode, Journal ofCardiovascular Electrophysiolgy, 1997, 8(9): 1031-45; Cheng, Y. N.,Mowrey, K. A., Van Wagoner, D. R., Tchou, P. J., Efimov, I. R., VirtualElectrode-Induced Reexcitation: A Mechanism of Defibrillation,Circulation Research, 1999, 85(11):1056-66; and Fishler, M. G.,Syncytial Heterogeneity as a Mechanism Underlying Cardiac Far-FieldStimulation During Defibrillation-Level Shocks. Journal ofCardiovascular Electrophysiology, 1998, 9(4): 384-94, all of which areincorporated herein by reference.

The ventricular defibrillation threshold (“DFT”) can be significantlydecreased by an orthogonally rotating current field. Tsukerman, B. M.,Bogdanov, Klu, Kon, M. V., Kriukov, V. A., Vandiaev, G. K.,Defibrillation of the Heart by a Rotating Current Field, Kardiologiia,1973, 13(12): 75-80, which is incorporated herein by reference.

Virtual electrode excitation can be used at local resistiveheterogeneities to depolarize a critical part of the reentry pathway orexcitable gap near the core of reentry. Thus, reentry can be terminateddirectly or destabilized and then the reentry can be terminated byadditional stimuli. This technique can be exploited in an implantable orexternal device, which, upon sensing a ventricular tachyarrhythmia, canapply the low energy stimulation. Also, the low energy stimulation canbe expected to be below the pain threshold and thus may cause no anxietyand uncomfortable side effects to the patient.

To further optimize the low energy method of termination, multipleelectric field configurations can be used to optimally excite theexcitable gap near the core of reentry and disrupt the reentrantcircuit. Referring to FIGS. 1A and 1B, schematic anterior and posteriorviews of a human heart and anatomical locations of implantabledefibrillation leads and sensing electrodes are depicted. As will bedescribed further below, shock pulses from a therapy first stage and asecond stage are applied between transvenous, implantable endocardialdefibrillation electrodes, including electrode 10 of lead 12 placed inthe right ventricle (RV), electrode 14 of lead 16 placed in the coronarysinus (CS), and electrode 18 of lead 16 placed in the left ventricularveins draining into the coronary sinus (LVC). As an alternative to LVC,a defibrillation patch 20 could be placed over the LV epicardium (LVP).One or multiple vectors will be used for energy delivery from electrodesin the RV, CS, and left ventricle (either LVC or LVP). Pacing stimuliapplied in a therapy third stage may be applied from the tip to coil ortip to ring of any of the RV, CS or LV leads.

Referring to FIGS. 2A to 2E, using three electrodes and the implantabledevice itself, the electric shock field can be continuously orincrementally rotated to effectively have a large number of combinationsfor selecting the shock vector. This includes reversing the shockpolarity between two electrodes. For example, each individual shockpulse may be directed through a different vector. The sequence ofswitching the vectors among shocks may also be changed, to create alarge number of possible electric fields between the RV, CS, and LVC (orLVP) defibrillation coils. In an embodiment, an optimization of thethree-stage therapy of the present invention will take place during alearning phase by a neural network of the device based on specific VTelectrogram morphologies in each patient.

Electric fields can be delivered between any two of these electrodes aswell as between one of these electrodes and the device itself.Modulation of the electric field vector can be used to achieve maximumcoverage of the heart and to maintain an optimal Virtual ElectrodePolarization pattern through the entire cycle of arrhythmia in order todepolarize the maximum area of excitable gaps. The optimal electricfields used and the correct sequence of fields can also be explored on atrial and error basis for each patient or can be estimated based onexternal information regarding potential sites of the reentrantcircuits, or can be based on a combination of both.

FIG. 2A depicts a pair of electric field shock vectors 30 a/b between anelectrode 10 in the RV and an electrode 14 in the CS (vector 30 a beingfrom the RV to the CS, and vector 30 b being from the CS to the RV);FIG. 2B depicts a pair of electric field vectors 32 a/b between anelectrode 10 in the RV and an electrode 18 in the LVC (vector 32 a beingfrom the RV to the LVC, and vector 32 b being from the LVC to the RV);FIG. 2C depicts a pair of electric field vectors 34 a/b between anelectrode 10 in the RV and to the “active/hot can” comprising animplantable device 24 (vector 34 a being from the RV to the device 24,and vector 34 b being from the device 24 to the RV); FIG. 2D depicts apair of electric field vectors 36 a/b between an electrode 10 in the RVand an electrode patch 20 at the LVP (vector 36 a being from the RV tothe LVP, and vector 36 b being from the LVP to the RV); and FIG. 2Edepicts a pair of electric field vectors 38 a/b between an electrodepatch 20 at the LVP to implantable device 24 (vector 38 a being from theLVP to device 24, and vector 38 b being from the device 24 to the LVP).

Multiple, monophasic shock pulses can be applied with intervals as afunction of arrhythmia cycle length. In one example, the far fieldunpinning shocks can be square waves, 10 ms in duration of which thevoltage and vectors will be varied to determine minimum terminationvoltage. In other embodiments, the far field unpinning shocks or pulsesmay be rounded, staggered, ascending, descending, biphasic, multiphasicor variations thereof.

While a number of lead and electrode placements are described above,generally speaking, an optimal electrode configuration is one thatmaximizes current density across the heart, particularly in the regionwhere the arrhythmia arises, thereby maximizing depolarization in theregion originating the arrhythmia.

An algorithm may be used for treatment of VT or VF. The device can firstestimate the mean CL of the arrhythmia. In addition, an algorithm can beused to characterize and categorize morphologies of a ventricularelectrogram in order to use this information for patient-specific andmorphology-specific optimization of phased unpinning far-field therapy.

An optimum time to apply the phased unpinning far-field therapy relativeto the cardiac cycle may be determined from ventricular sensingelectrodes including RV or far-field R-wave detection. Examples offinding unsafe times for far-field shock are also described in U.S. Pat.No. 5,814,081.

Other timing considerations, particularly with respect to phase or stagedurations, may be determined in whole or in part by characteristics ofthe sensed ventricular tachyarrhythmia (VT or VF). As will be describedbelow, ventricular activity, such as R-wave characteristics, may be usedto determine an overall therapy timing, such as a maximum window of timefor therapy delivery.

Learning algorithms may also used to optimize therapy on subsequentterminations. Once the optimal timing and field settings are achievedfor a patient to terminate a ventricular tachyarrhythmia, these settingsmay be the starting point for termination of the next occurrence of VF.

In some embodiments, therapy can be optimized using a trial and errorapproach combined with learning algorithms to tailor therapy for eachpatient. The optimization includes two objectives: (a) terminatingtachycardia and (b) avoiding intensities associated with pain.

As described above, the pain threshold depends on many factors,including autonomic tone, presence of drugs, location of electrodes andshock waveforms. A value of 0.1 J has been reported by Ladwig, K. H.,Marten-Mittag, B., Lehmann, G., Gundel, H., Simon, H., Alt, E., Absenceof an Impact of Emotional Distress on the Perception of IntracardiacShock Discharges, International Journal of Behavioral Medicine, 2003,10(1): 56-65, which is incorporated herein by reference, as the energyvalue where pain and/or discomfort is first generally experienced.However, it can be different from patient to patient. Thus, a real-timefeedback to the patient can be provided in estimating the pain thresholdduring either the implantation or calibration of the device or duringexecution of the optimizing learning algorithms.

In one embodiment, the morphology of an arrhythmia's electrogram can bedocumented, stored, and compared to previously stored morphologies.Anatomic location(s) of the reentry circuit(s) are determined by thespecific anatomy and physiological remodeling of the ventricle, whichare unique for each patient. Thus, the morphologies can reveal thespecific anatomic locations of the reentry circuits. Optimization of thepulse sequence of the therapy can be conducted separately for eachelectrogram morphology and stored in memory for future arrhythmiaterminations.

Because this device, in certain embodiments, can deliver a series ofelectric field stimuli in rapid succession, traditional implantablepulse generators, such as those normally used in ICDs generally may beinadequate for the device. Traditional implantable pulse generatorsemploy a charging period (on the order of seconds) to charge acapacitor, then rapidly discharge the capacitor to apply the shock.Before the next shock application, the capacitor may need to be chargedagain. In this device, several low energy far field unpinningshocks/pulses (two-ten) can be applied in rapid succession, which insome embodiments is determined by the VT or VF cycle length (CL) foreach unpinning shock.

The implantable pulse generator according to one type of embodiment ofthis device can include several smaller capacitors that charge before orduring the defibrillation trials. For each stimulus delivered, a singlecapacitor discharges with the appropriate amount of energy followedsequentially by a discharge from another capacitor until the appropriatenumber of stimuli is delivered. The capacitors can all be chargedsimultaneously before the entire defibrillation trial or, alternatively,the capacitors can be charged sequentially in groups, or individually.In one example implementation, capacitors which are used for unpinningshocks are charged while other unpinning shocks are applied. In arelated example, a capacitor that is used for an earlier unpinning shockis re-charged during a subsequent one or more shock, and is furtherre-used for a later unpinning shock. This latter example is facilitatedin embodiments where the power supply is capable of sufficient currentdrive to charge the capacitors in sufficient time to permit their re-usewithin the same trial.

In a related embodiment, the device uses multiple capacitors for storingthe electrotherapy energy, except that, unlike the example embodimentdescribed above, each capacitor has sufficient energy storage to providemore than a single shock in the sequence.

In order to produce the appropriate stimuli across the appropriate leadconfiguration, a fast-switching network can be employed to switch thedischarged energy between the different capacitors as well as switchingthe applied energy to the correct electrodes. The pretreatment of pulsesis described further in U.S. Pat. Nos. 5,366,485 and 5,314,448, both ofwhich are incorporated herein by reference.

It is contemplated that the method of the present invention can beutilized together with, or separate from, other pacing anddefibrillation therapies. For example, the present invention can beimplemented as part of an ICD where a high voltage defibrillation shockcan be delivered in the event that the method of the present inventionis unable to successfully convert a cardiac arrhythmia. Alternatively,the present invention could be implemented as part of a conventionalpacemaker to provide for an emergency response to a VT/VF condition inthe patient that would increase the chances of patient survival.

The methods of the present invention also contemplate the use of anynumber of arrangements and configurations of waveforms and waveshapesfor the electrical stimulation pulse(s). Known monophasic, biphasic,triphasic and cross-phase stimulation pulses may be utilized. In oneembodiment, the present invention contemplates the use of an ascendingramp waveform as described in the article Qu, F., Li, L., Nikolski, V.P., Sharma, V., Efimov, I. R., Mechanisms of Superiority of AscendingRamp Waveforms: New Insights into Mechanisms of Shock-inducedVulnerability and Defibrillation, American Journal of Physiology—Heartand Circulatory Physiology, 2005, 289: H569-H577, the disclosure ofwhich is incorporated herein by reference.

The methods of the present invention also contemplate the use of anynumber of arrangement and configurations for the generation of thephased unpinning far field electrical stimulation pulse(s). Whileconventional high voltage capacitor discharge circuitry may be utilizedto generate the lower energy stimulation pulse(s) in accordance with thepresent invention, it is also expected that alternative arrangementscould be utilized involving lower voltage capacitor arrangements, suchas stacked, switched or secondary capacitors, rechargeable batteries,charge pump and voltage booster circuits as described, for example, inU.S. Pat. Nos. 5,199,429, 5,334,219, 5,365,391, 5,372,605, 5,383,907,5,391,186, 5,405,363, 5,407,444, 5,413,591, 5,620,464 and 5,674,248, thedisclosures of each of which are incorporated herein by reference.Generation of the staged/phased unpinning far field therapy inaccordance with embodiments of the present invention can be accomplishedby any number of methods, including known methods for generating pacingpulses. Similarly, any number of known techniques for cardiac arrhythmiadetection may be used in accordance with the method of the presentinvention.

In accordance with one embodiment the PUFFT three-stage therapy isdelivered as part of a three-stage ventricular therapy. As shown in FIG.3, in one embodiment the three-stage therapy of the present inventioncomprises a three-stage ventricular cardioversion and defibrillationtherapy delivered to the patient in response to detection of aventricular arrhythmia, the three-stage ventricular therapy having a setof therapy parameters and having a first stage (400) and a second stage(402) delivered via a far field configuration of the electrodes and athird stage (404) delivered via a near field configuration of theelectrodes.

It will be understood that “three stage” ventricular therapy refers toall variations of therapies of the claimed invention that include atleast one set of first-stage pulses, at least one set of second-stagepulses, and at least one set of third-stage pulses. It will also beunderstood that “multi-therapy” includes multiple three-stage therapies,wherein the ventricular arrhythmia may be reevaluated betweenthree-stage therapy implementations.

Referring to FIG. 4, a combined representation of three of the stages ofthe three-stage ventricular therapy is shown. A first stage (400) isapplied for unpinning of one or more singularities associated with aventricular arrhythmia. A second stage (402) is applied foranti-repinning of the one or more singularities associated with theventricular arrhythmia. A third stage (404) is applied for extinguishingof the one or more singularities associated with the ventriculararrhythmia.

In various embodiments, the first stage (400) has at least two and up toten ventricular cardioversion/defibrillation pulses of 2 volts to 100volts. In other embodiments, particularly for VF pulse voltage may be ashigh as 200 volts, and in other embodiments as high as 400 volts, butstill with an overall therapy energy significantly lower thantraditional therapies. While depicted as monophasic, first stage (400)pulses may alternatively comprise biphasic or other multiphasic pulses.Pulse duration may be approximately 3-4 milliseconds in someembodiments, or, more generally, equal to or less than 10 millisecondsin various other embodiments. In an embodiment, first stage (400) pulsesare delivered within one or two VT/VF cycle lengths.

In some embodiments, the arrhythmia will be reassessed after applyingfirst stage (400) pulses. In other embodiments, the arrhythmia will notbe reassessed until all stages of the therapy have been delivered.

In an embodiment, an interstage delay (I1) of 50 to 800 millisecondsprecedes the second stage (402), though in other embodiments, interstagedelay I1 may be shorter or longer.

In some embodiments, the second stage (402) comprises six to tenultra-low energy monophasic or multiphasic far field pulses. In anembodiment, the minimum voltage amplitude of second stage (402) pulsesis set to the ventricular shock excitation threshold (vSET), defined asthe minimum voltage at which a far field pulse captures (excites) theventricle. Typical shock pulse voltage for this stage is 0.5 to 20V.Though depicted as monophasic pulses, second stage (402) may comprisemultiphasic or another non-traditional configuration. In an embodiment,second-stage pulse duration ranges from 5 ms to 20 milliseconds with apulse coupling interval ranging from 70% to 100% of the cycle length ofthe ventricular tachycardia or ventricular fibrillation cycle length(VT/VF CL).

In some embodiments, the tachyarrhythmia will be reassessed afterapplying first stage (400) and second stage (402) pulses. In otherembodiments, the tachyarrhythmia will not be reassessed until all stagesof the therapy have been delivered.

An interstage delay (I2) of between 50 to 800 milliseconds precedes thethird stage (404), though in other embodiments, interstage delay I2 maybe shorter or longer.

In some embodiments, the third stage (404) comprises eight to twelvenear-field pacing stimuli, a near-field entrainment, which facilitatesthe previous two stages to drive the tachyarrhythmia to termination.Though depicted as monophasic pulses, third stage (404) may comprisemultiphasic or another non-traditional configuration. In an embodiment,third stage (404) pulses are applied through an endocardialdefibrillation/pacing electrode at 2-4 times the strength of thediastolic pacing threshold, with a pulse duration of more than 0.2 andless than 5 milliseconds, and a pulse coupling interval of 70 to 100% ofthe VT/VF CL.

Referring to FIG. 5, an embodiment of first stage (400) is shown. Inthis embodiment, each of five monophasic pulses is delivered from aseparate output capacitor arrangement where an H-bridge output switchingarrangement reversals the polarity of the far-field electrodes at somepoint during the discharge of the output capacitor arrangement. Inalternate embodiments, fewer output capacitor arrangements may be usedwhere later cardioversion pulses are delivered from the same outputcapacitor arrangement that was used to delivery an earlier cardioversionpulse and that has been recharged before the later cardioversion pulse.In other embodiments, each phase of the biphasic cardioversion pulse maybe delivered from a separate output capacitor arrangement. In otherembodiments, a switching capacitor network may be used to combine outputcapacitor arrangements to deliver the cardioversion pulses of the firststage (400). It will be understood that the initial output voltage,reversal voltage (in the case of an alternative biphasic pulse),duration and coupling interval between pulses may be the same ordifferent for all or for some of the pulses within the range of pulseparameters provided for the first stage (400). It will also beunderstood that the pulses shown in FIG. 5 of the first stage (400) mayall be delivered through the same far-field electrode configuration, andin other embodiments the pulses may be delivered as part of a rotatingset of PUFFT pulses delivered through different far-field electrodeconfigurations.

Referring to FIG. 6, an embodiment of the second stage (402) is shown.In this embodiment, each of six monophasic far-field low voltage pulsesare delivered from the same output capacitor arrangement that isrecharged between successive pulses, although the pulses may each bedelivered from separate output capacitor arrangements or from feweroutput capacitor arrangements than the total number of pulses in thesecond stage (402). Alternatively, the pulses may be delivered directlyfrom a charge pump, voltage booster or other similar kind of chargestorage and/or delivery arrangement powered by a battery system. As withthe first stage (400), it will be understood that the initial outputvoltage, duration and coupling interval between pulses of the secondstage (402) may be the same or different for all or for some of thepulses within the range of pulse parameters provided for the secondstage (402). It will also be understood that the pulses shown in FIG. 6of the second stage (402) may all be delivered through the samefar-field electrode configuration, and in other embodiments the pulsesmay be delivered as part of a rotating set of PUFFT pulses deliveredthrough different far-field electrode configurations. The far-fieldelectrode configuration for the second stage (402) may be the same as,or different than, the far-field electrode configuration utilized forthe first stage (400).

Referring to FIG. 7, an embodiment of the third stage (404) is shown. Inthis embodiment, each of eight monophasic near-field low voltage pulsesare delivered from the same output capacitor arrangement that isrecharged between successive pulses, although the pulses may each bedelivered from separate output capacitor arrangements or from feweroutput capacitor arrangements than the total number of pulses in thethird stage (404). Alternatively, the pulses may be delivered directlyfrom a charge pump, voltage booster or other similar kind of chargestorage arrangement powered by a battery system. In one embodiment, thesame output capacitor arrangement is used to deliver the second stagepulses and the third stage pulses. As with the first stage (400) andsecond stage (402), it will be understood that the initial outputvoltage, duration and coupling interval between pulses of the thirdstage (404) may be the same or different for all or for some of thepulses within the range of pulse parameters provided for the third stage(404). It will also be understood that the pulses shown in FIG. 14 ofthe third stage (404) may all be delivered through the same near-fieldelectrode configuration, and in other embodiments the pulses may bedelivered as part of a rotating set of PUFFT pulses delivered throughdifferent near-field electrode configurations. In some embodiments, thenear-field electrode configuration may be a monopolar electrodearrangement, and in other embodiments, the near-field electrodeconfiguration may be a bipolar electrode arrangement.

Referring to FIGS. 8 and 9, an alternate embodiment of the three-stageventricular cardioversion/defibrillation therapy is shown. In thisembodiment, the unpinning first stage (400) and anti-repinning secondstage (402) are each repeated in sequence as part of the overallventricular therapy (28) before delivery of the extinguishing thirdstage (404). As with the embodiment shown in FIG. 4, the parameters foreach of the stages, and each of the pulses within each stage, may be thesame or different for different stages and/or different pulses withineach stage.

Referring to FIGS. 10 and 11, an alternate embodiment of the three-stageventricular cardioversion/defibrillation therapy is shown. In thismulti-therapy embodiment, the unpinning stage 1 (400) and anti-repinningstage 2 (402), as well as the extinguishing stage 3 (404) are eachrepeated in sequence as part of the overall ventricularcardioversion/defibrillation therapy (28), followed by a repeateddelivery of all three of the stages before completion of the ventricularcardioversion/defibrillation therapy (28). As with the embodiment shownin FIG. 4, the parameters for each of the stages, and each of the pulseswithin each stage, may be the same or different for different stagesand/or different pulses within each stage.

As described above, the three-stage ventricular therapy of the presentinvention may use various combination of each of the individual first,second, and three stages, depending on the different types ofarrhythmias and morphology of ventricular electrograms. For example, thefirst stage and the second stage can be repeated several times, and thenfollowed by the third stage, as depicted and described with respect toFIGS. 8 and 9. Consequently, combinations include, but are not limitedto (referring to stages): 1-2-3; 1-2-1-2-3; 1-1-2-2-3-3, and so on.

Referring now to FIGS. 12A and 12B, a detailed description of theconstruction of an embodiment of the three-stage ventricularcardioversion/defibrillation system is described. In the exampleembodiment depicted in FIG. 12A at a high level, a ventriculararrhythmia treatment apparatus 500 includes a plurality of electrodes502 adapted to be implanted proximate a ventricle of a heart of apatient to deliver far field pulses and a plurality of electrodes 504adapted to implanted proximate the ventricle of the heart of the patientto deliver near field pulses and sense cardiac signals. The housing ofapparatus 500 can serve as one of the far-field electrodes 502 ornear-field electrodes 504. Additionally, far-field electrodes 502 andnear-field electrodes 504 can share at least one common electrode insome embodiments. An implantable therapy generator 506 is operablyconnected to the electrodes and includes a battery system 508 (or othersuitable on-board energy source such as super capacitors, for example)and one or more power supply circuits 510 operably coupled and providingpower to sensing circuitry 512, detection circuitry 514, controlcircuitry 516 and therapy circuitry 518 of the implantable therapygenerator. In one type of embodiment, therapy circuitry 518 includes aspecialized power supply that is fed directly from battery system 508,bypassing power supply circuitry 510. Sensing circuitry 512 sensescardiac signals representative of ventricular activity. Detectioncircuitry 514 evaluates the cardiac signals representative ofventricular activity to determine a ventricular cycle length and detecta ventricular arrhythmia based at least in part on the ventricular cyclelength. Control circuitry 516, in response to the ventriculararrhythmia, controls generation and selective delivery of a three-stageventricular therapy to electrodes 502 and 504, with each stage having aninter-stage delay of 50 to 800. In various embodiments, detectioncircuitry 514, control circuitry 516 and therapy circuitry 518 can sharecomponents. For example, in one embodiment, a common microcontroller canbe a part of detection circuitry 514, control circuitry 516 and therapycircuitry 518.

The therapy circuitry 518 is operably connected to electrodes 502 and504 and control circuitry 516. FIG. 12B illustrates an examplearrangement of therapy circuitry 518 according to one type ofembodiment. Therapy circuitry 518 can include its own power supplycircuit 602, which is fed from battery system 508. Power supply circuit602 can be a simple voltage regulator, or it can be a current limitingcircuit that functions to prevent therapy circuitry (which has thegreatest power demands of all the circuitry in the device) from drawingtoo much power and, consequently, causing a drop in the supply voltagebelow a sufficient level to power the controller and other criticalcomponents. Alternatively, power supply circuit 602 can be implementedin power supply circuit 510; or, in one type of embodiment, power supplycircuit 602 can be omitted entirely, such that charging circuit 604 isfed directly from battery system 508.

Charging circuit 604 is a voltage converter circuit that producesvoltages at the levels needed for the stimulation waveform. The input tocharging circuit is a voltage at or near the voltage of battery system508, which in one embodiment is between 3 and 12 volts. Since thestimulation waveform, particularly the first stage, is at a much highervoltage, up to around 100 volts, a boosting topology is used forcharging circuit 604. Any suitable boosting circuit may be employed tothis end, including a switching regulator utilizing one or moreinductive elements (e.g., transformer, inductor, etc.), or a switchingregulator utilizing capacitive elements (e.g., charge pump).

FIGS. 13A-13F illustrate various known topologies for voltage boostingcircuits that can be utilized as part of charging circuit 604 accordingto various embodiments. FIG. 13A illustrates a basic boost convertertopology. The boost converter of FIG. 20A utilizes a single inductorindicated at L1 to store energy in each cycle of switch SW. When switchSW closes, inductor L1 is energized and develops a self-induced magneticfield. When switch SW opens, the voltage at the L1-SW-D1 node is boostedas the magnetic field in inductor L1 collapses. The associated currentpasses through blocking diode D1 and charges energy storage capacitorC_(out) to a voltage greater than input voltage V_(in).

FIG. 13B illustrates a flyback converter topology. The flyback converterutilizes transformer T1 as an energy storage device as well as a step-uptransformer. When switch SW is closed, the primary coil of transformerT1 is energized in similar fashion to inductor L1 of FIG. 13A. Whenswitch SW opens, the voltage across the primary coil is reversed andboosted due to the collapsing magnetic field in the primary. Thechanging voltages of the primary coil are magnetically coupled to thesecondary coil, which typically has a greater number of windings tofurther step-up the voltage on the secondary side. A typical turns ratiofor defibrillator signal applications in certain embodiments is Np:Ns ofabout 1:15, where Np is the number of primary turns and Ns is the numberof secondary turns. The high voltage across the secondary coil isrectified by the diode and stored in capacitor C_(out).

FIG. 13C illustrates a single ended primary inductance converter(“SEPIC”), which offers certain advantages over other power convertertopologies. For instance, the SEPIC converter offers an advantage of notrequiring significant energy storage in the transformer. Since most ofthe energy in a transformer is stored in its gap, this reduces the gaplength requirement for the transformer. Battery voltage is applied atVIN and the switching element is switched at a fixed frequency and aduty cycle that is varied according to feedback of battery current intothe power converter and output voltage. Voltage from the output of thestep up transformer (T1) is rectified by the diode D1 to generate outputvoltage on C_(out).

FIG. 13D illustrates a variation of the SEPIC converter of FIG. 13C. TheSEPIC topology of FIG. 13D has an additional inductive component (L1).The additional inductor L1 can be implemented either discretely, or canbe magnetically coupled with the high voltage transformer into a singlemagnetic structure, as depicted in FIG. 13D.

FIG. 13E illustrates a Cuk converter topology. A Cuk converter comprisestwo inductors, L1 and L2, two capacitors, C₁ and C_(out), switch SW, anddiode D1. Capacitor C is used to transfer energy and is connectedalternately to the input and to the output of the converter via thecommutation of the transistor and the diode. The two inductors L1 and L2are used to convert, respectively, the input voltage source (V_(i)) andthe output voltage at capacitor C_(out) into current sources. Similarlyto the voltage converter circuits described above, the ratio of outputvoltage to input voltage is related to the duty cycling of switch SW.Optionally, inductors L1 and L2 can be magnetically coupled as indicatedT1*.

FIG. 13F illustrates a basic charge pump topology for multiplying theinput voltage. The example shown is a Cockcroft-Walton multiplyingcircuit. Three capacitors (C_(A), C_(B), and C_(C)), each of capacity C,are connected in series, and capacitor C_(A) is connected to the supplyvoltage, V_(DD). During phase φ, capacitor C₁ is connected to C_(A) andcharged to voltage V_(DD).

When the switches change position during the next cycle, φ_(b),capacitor C₁ will share its charge with capacitor C_(B), and both willbe charged to V_(DD)/2 if they have equal capacity. In the next cycle,C₂ and C_(B) will be connected and share a potential of V_(DD)/4, whileC₁ is once again charged to V_(DD). As this process continues for a fewcycles, charge will be transferred to all the capacitors until apotential of 3V_(DD) is developed across the output Vout. Additionalstages may be added to increase the voltage multiplication.

Referring again to FIG. 12B, pulse energy storage circuit 606 can takevarious forms. Generally, pulse energy storage circuit has energystorage capacity sufficient to store either all three stages of theventricular therapy, or a portion of the therapy's energy, provided thatthe arrangement of energy storage circuit 606 and charging circuit 604supports the ability to re-charge portions of the energy storage circuit606 while other portions thereof are discharging or are about todischarge during application of the electrotherapy. FIG. 13G illustratesa basic example of energy storage circuit 606, in which there are threeseparate storage reservoirs for each of the three stages of theelectrotherapy. Storage reservoir 606 a stores the energy for the firststage; storage reservoir 606 b for the second; and 606 c for the third.Each storage reservoir can have one, or a plurality of storage elements.In one type of embodiment, each storage reservoir has a plurality ofstorage element groups, with each storage element group individuallyswitchably selectable for charging and discharging. The storage elementscan take any suitable form, including capacitors of a suitabletechnology, e.g., electrolytic, tantalum film, ceramic chip, supercap,or the like.

Storage reservoirs 606 a-606 c are coupled to charging circuit 604 viaselector switch 607. Selector switch 607 can be implemented with aanalog multiplexer, transmission gates, or any other suitable electronicswitching arrangement. Selector switch 607 is controlled by controllercircuit 614 in this example.

Referring again to FIG. 12B, wave shaping circuit 608 regulates theapplication of the electrotherapy by selecting, and controlling thedischarging of the energy stored in energy storage circuit 606. In oneembodiment, wave shaping circuit 608 is in the form of a H-bridgetopology, as illustrated in FIG. 13G. Switches S1-S4 are individuallycontrolled by controller circuit 614. The H-bridge topology facilitatessteering, or reversing the polarity, of the electrotherapy signals,enabling a biphasic shock to be applied from a single-polarity energystorage reservoir. Other forms of switchable coupling are alsocontemplated for other embodiments. For instance, a set of analogtransmission gates can be used, such that each storage reservoir 606a-606 c is individually selectable. In this latter example, separatecapacitors of opposite polarity are used for storing the charge for eachphase of the biphasic unpinning waveform of the first electrotherapyphase.

Referring again to FIG. 12B, electrode coupling circuit 610 operates toselect which of the multiple sets of patient electrodes 612 are coupledto the output of the wave shaping circuit 608. Electrode couplingcircuit 610 can be implemented in one example embodiment using a set ofanalog multiplexers that are controlled by controller circuit 614.

In various other embodiments, the functionality of charging circuit 604and pulse energy storage circuit 606 can be combined into a singlecircuit 620, such as a charge pump arrangement, in which certain ones ofthe capacitors are also used for both, building up charge, and storingthe pulse energy for the electrotherapy. In another variation, the pulseenergy storage circuit 606 can be one and the same circuit, as the waveshaping circuit 608, depicted at 622, such as, for example, wheremultiple different capacitors are used to store each individual pulse,and where the electrode coupling circuit has the capability toindividually select which capacitors are switched in to whichelectrodes. Moreover, in yet another variation, charging circuit 604,pulse energy storage circuit 606, and wave shaping circuit 608 can becombined as a single circuit implementation 624, which can beimplemented as a combination of circuits 620 and 622.

Referring to FIG. 14, results of an experimental application of thethree-stage ventricular therapy as administered in a clinical study aredepicted.

Two vectors to defibrillate ventricular tachyarrhythmias in caninesusing multiple stage electrotherapy were studied. The two vectors were(i) RV to CS and (ii) RV to left ventricular epicardial patch (LVP). Asdepicted in FIG. 14, multiple-stage electrotherapy delivered from theRV-CS vector significantly reduced the defibrillation threshold comparedto a single biphasic shock with respect to total energy.

As described above, current implantable defibrillators use a high-energybiphasic (BP) shock to terminate ventricular tachycardia (VT) whenanti-tachycardia pacing (ATP) fails. In this study, a three-stageelectrotherapy as described above, was compared to a single biphasicshock, delivered via a fully endocardial lead system (refer also toFIGS. 1A and 1B).

Myocardial infarction was induced in mongrel dogs (n=3). Four dayslater, endocardial bipolar pace/shock leads were placed in the rightventricle (RV) apex and coronary sinus (CS). A patch (LVP) was placedover the posterolateral left ventricle. ATP (8 pulses, 88% of the VTcycle length (CL)) were administered via the RV bipole after sustainedVT induction. If ATP failed, cardioversion thresholds (CVT) of thethree-stage and single biphasic shock were measured. The three-stagetherapy consisted of sequentially administering first stage (400),second stage (402), and third stage (404) as follows: three monophasicshock pulses delivered within one VT CL (first stage); six monophasicshock pulses delivered with an interval of 88% of the VT CL at theventricular capture voltage (second stage), and ATP (third stage). RV-CScoil and RV-LVP shock vectors were compared.

Results indicated that the average CL of sustained VT was 148±26 ms. Thesuccess rate of ATP alone was 7.04%. The RV-CS shock vector had lowerimpedance than RV-LVP (54.4±18.1 Ohms versus 109.8±16.9 Ohms,respectively, p<0.001). The three-stage therapy delivered from the RV-CSvector significantly reduced the CVT compared to a single biphasic shockwith respect to total energy (0.03±0.05 J versus 2.37±1.20 J,respectively, p<0.001) and peak shock voltage (7.2±6.9 V versus137.7±43.8 V, respectively, p<0.001).

Consequently, the three-stage electrotherapy terminated ATP-resistant VTwith significantly lower peak voltage and total energy compared to aconventional single biphasic shock. As such, this novel electrotherapyprovides a low-voltage, low-energy alternative to high-energy ICD shockswhen ATP fails, and can be delivered through a fully implantableendocardial lead system. Further, this therapy may enable device-basedpainless ventricular defibrillation by defibrillating at thresholdsbelow the human pain threshold.

The embodiments above are intended to be illustrative and not limiting.Additional embodiments are within the claims. In addition, althoughaspects of the present invention have been described with reference toparticular embodiments, those skilled in the art will recognize thatchanges can be made in form and detail without departing from the spiritand scope of the invention, as defined by the claims.

Persons of ordinary skill in the relevant arts will recognize that theinvention may comprise fewer features than illustrated in any individualembodiment described above. The embodiments described herein are notmeant to be an exhaustive presentation of the ways in which the variousfeatures of the invention may be combined. Accordingly, the embodimentsare not mutually exclusive combinations of features; rather, theinvention may comprise a combination of different individual featuresselected from different individual embodiments, as understood by personsof ordinary skill in the art.

Any incorporation by reference of documents above is limited such thatno subject matter is incorporated that is contrary to the explicitdisclosure herein. Any incorporation by reference of documents above isfurther limited such that no claims included in the documents areincorporated by reference herein. Any incorporation by reference ofdocuments above is yet further limited such that any definitionsprovided in the documents are not incorporated by reference hereinunless expressly included herein.

For purposes of interpreting the claims for the present invention, it isexpressly intended that the provisions of Section 112, sixth paragraphof 35 U.S.C. are not to be invoked unless the specific terms “means for”or “step for” are recited in a claim.

The invention claimed is:
 1. A ventricular arrhythmia treatmentapparatus, comprising: at least one electrode adapted to be implantedproximate a ventricle of a heart of a patient to deliver far fieldpulses; at least one electrode adapted to implanted proximate theventricle of the heart of the patient to deliver near field pulses andsense cardiac signals; an implantable therapy generator adapted to beimplanted in a patient and operably connected to the electrodes,including: sensing circuitry that senses cardiac signals representativeof ventricular activity; detection circuitry operably connected to thesensing circuitry to evaluate the cardiac signals representative ofventricular activity to determine a ventricular cycle length and detecta ventricular arrhythmia based at least in part on the ventricular cyclelength; control circuitry operably connected to the sensing circuitrythat, in response to the ventricular arrhythmia, controls generation andselective delivery of a three-stage ventricular therapy to theelectrodes with each stage having an inter-stage delay of between 50 to800 milliseconds; and therapy circuitry operably connected to theelectrodes and the control circuitry including: at least one first stagecharge storage circuit selectively coupled to the at least one far fieldelectrode that selectively stores energy for a first stage of thethree-stage ventricular therapy having at least two and not more thanten ventricular pulses of at least 2 volts and not more than 100 voltsto unpin one or more singularities associated with the ventriculararrhythmia; at least one second stage charge storage circuit selectivelycoupled to the at least one far field electrode that selectively storesa second stage of the three-stageventricular therapy having at least sixand not more than ten far field pulses of less than a ventricularfar-field excitation threshold with a pulse coupling interval of between70-100% of the cycle length of the ventricular arrhythmia after thefirst stage therapy is applied, wherein the second stage preventsrepinning of the one or more singularities associated with theventricular arrhythmia that are unpinned by the first stage; and atleast one third stage charge delivery circuit selectively coupled to thenear field electrode that selectively delivers a third stage of thethree-stage cardioversion therapy having at least eight and not morethan twelve near field pulses at a voltage substantially ranging fromtwo to four times the diastolic pacing threshold, with a pulse couplinginterval of between 70-100% of the cycle length of the ventriculararrhythmia, wherein the third stage extinguishes the one or moresingularities associated with the ventricular arrhythmia that areunpinned by the first stage and prevented from repining by the secondstage; and a battery system operably coupled and providing power to thesensing circuitry, the detection circuitry, the control circuitry andthe therapy circuitry.
 2. The apparatus of claim 1, wherein the firststage pulses are monophasic pulses.
 3. The apparatus of claim 1, whereinthe first stage consists of three to five pulses.
 4. The apparatus ofclaim 1, wherein the three-stage ventricular therapy delivers less than0.1 J in total.
 5. The apparatus of claim 1, wherein the third stagecharge delivery circuit comprises a charge pump.
 6. The apparatus ofclaim 1, wherein the third stage charge delivery circuit comprises atleast one capacitor.
 7. The apparatus of claim 1, wherein the firstcharge storage circuit includes at least one output capacitorconfiguration and a high voltage transformer electrically coupled to thebattery system to charge the at least one output capacitorconfiguration.
 8. The apparatus of claim 1, wherein the first chargestorage circuit includes at least one output capacitor configuration anda charge pump electrically coupled to the battery system to charge theat least one output capacitor configuration.
 9. The apparatus of claim1, wherein the second charge storage circuit and third charge storagecircuit include a single low voltage output capacitor configuration andswitching circuitry between the single low voltage output capacitorconfiguration and the far field electrodes and the near fieldelectrodes.
 10. The apparatus of claim 1, wherein the control circuitryincludes an H-bridge switching circuit operably connected to theelectrodes to enable delivery of biphasic pulses.
 11. The apparatus ofclaim 1, wherein the control circuitry controls delivery of thethree-stage ventricular therapy to deliver in sequence one of the firststage, one of the second stage and one of the third stage.
 12. Theapparatus of claim 1, wherein the control circuitry controls delivery ofthe three-stage ventricular therapy to deliver in sequence one of thefirst stage, one of the second stage, one of the first stage, one of thesecond stage and one of the third stage.
 13. The apparatus of claim 1,wherein the apparatus and the at least two leads include at least fourfar-field electrodes and the control circuitry is configured toselectively excite combinations of the far-field electrodes to create aplurality of different electric fields between different ones of thefar-field electrodes to deliver a rotating set of electrical fields as aphased unpinning far-field therapy generated by the at least one firststage charge storage circuit and the at least one second stage chargestorage circuit.
 14. The apparatus of claim 1, wherein the controlcircuitry comprises a microprocessor programmed with a heuristiclearning algorithm that dynamically modifies settings of the set oftherapy parameters for the pulses of each stage in response to aneffectiveness of the three-stage ventricular therapy.
 15. A ventriculararrhythmia treatment apparatus, comprising: an implantable therapygenerator adapted to be implanted in a patient, including: means fordetecting a ventricular arrhythmia and determining a cycle length of theventricular arrhythmia; means for generating a three-stage ventriculartherapy, including: means for generating a first stage of thethree-stage ventricular therapy having at least two and not more thanten monophasic ventricular pulses of at least 2 volts and not more than100 volts for unpinning of one or more singularities associated with aventricular arrhythmia; means for generating a second stage of thethree-stage atrial cardioversion therapy having at least six and notmore than ten far field pulses of less than a ventricular far-fieldexcitation threshold with a pulse coupling interval of between 70-100%of the cycle length of the ventricular arrhythmia for anti-repinning ofthe one or more singularities associated with the ventriculararrhythmia; and means for generating a third stage of the three-stagecardioversion therapy having at least eight and not more than twelvenear field pulses at a voltage substantially ranging from two to fourtimes the diastolic pacing threshold with a pulse coupling interval ofbetween 70-100% of the cycle length of the atrial arrhythmia forextinguishing of the one or more singularities associated with theventricular arrhythmia; and means for controlling delivery of thethree-stage ventricular therapy in response to detection of theventricular arrhythmia with each stage having an inter-stage delay ofbetween 50 to 800 milliseconds; and at least two leads adapted to beoperably connected to the implantable therapy generator, each leadhaving at least one electrode adapted to be positioned proximate aventricle of a heart of the patient through which the three-stageventricular therapy is selectively delivered to the ventricle of theheart, such that the means for generating the first stage and the meansfor generating the second stage are selectively coupled by the means forcontrolling delivery to a far-field configuration of the electrodes andthe means for generating the third stage are selectively coupled by themeans for controlling delivery to a near-field configuration of theelectrodes.
 16. The apparatus of claim 15, wherein the means forcontrolling delivery of the three-stage ventricular therapy delivers insequence one of the first stage, one of the second stage and one of thethird stage.
 17. The apparatus of claim 15, wherein the means forcontrolling delivery of the three-stage ventricular therapy delivers insequence one of the first stage, one of the second stage, one of thefirst stage, one of the second stage and one of the third stage.
 18. Theapparatus of claim 15, wherein the apparatus and the at least two leadsinclude at least four far-field electrodes and the means for controllingdelivery of the three-stage ventricular therapy is configured toselectively excite combinations of the far-field electrodes to create aplurality of different electric fields between different ones of thefar-field electrodes to deliver a rotating set of electrical fields as aphased unpinning far-field therapy generated by the means for generatingthe first stage and the means for generating the second stage.
 19. Theapparatus of claim 15, wherein the means for controlling deliveryfurther comprises a heuristic learning algorithm that dynamicallymodifies settings of the set of therapy parameters for the pulses ofeach stage in response to an effectiveness of the three-stageventricular therapy.
 20. The apparatus of claim 15, wherein the meansfor generating the three-stage ventricular therapy includes a batterysystem and the means for generating the first stage includes at leastone output capacitor configuration and a high voltage transformerelectrically coupled to the battery system to charge the at least oneoutput capacitor configuration.
 21. The apparatus of claim 15, whereinthe means for generating the three-stage ventricular therapy includes abattery system and the means for generating the first stage includes atleast one output capacitor configuration and a charge pump electricallycoupled to the battery system to charge the at least one outputcapacitor configuration.
 22. The apparatus of claim 21, wherein themeans for generating the first stage includes a plurality of outputcapacitor configurations, one for each biphasic ventricular pulse, andthe charge pump alternatively trickle charges each of the plurality ofoutput capacitor configurations.
 23. The apparatus of claim 15, whereinthe at least two leads include a first lead having at least onefar-field electrode and a second lead having at least one near-fieldelectrode, and wherein the implantable pulse generator includes at leasta portion of a housing of the implantable pulse generator that serves asa far-field electrode.
 24. A method of treating ventricular arrhythmiascomprising: (a) causing a ventricular arrhythmia treatment device to bemanufactured and made available to a user, ventricular arrhythmiatreatment device including an implantable therapy generator adapted togenerate and selectively deliver a three-stage ventricular therapy andat least two leads operably connected to the implantable therapygenerator, each lead having at least one electrode adapted to bepositioned proximate the ventricle of a heart of the patient; (b)causing a ventricular arrhythmia treatment device to be manufactured andmade available to a user; providing instructions for implanting theventricular arrhythmia treatment device in a patient during a surgicalprocedure; (c) causing a ventricular arrhythmia treatment device to bemanufactured and made available to a user; providing instructions forconfiguring the ventricular arrhythmia treatment device at a time aftercompletion of the surgical procedure, including instructions forprogramming the ventricular arrhythmia treatment device with a set oftherapy parameters for delivering a three- stage ventricular therapy toa patient via both a far-field configuration and a near-fieldconfiguration of the electrodes upon detection of a ventriculararrhythmia by the ventricular arrhythmia treatment device, wherein thethree-stage ventricular therapy includes: a first stage of thethree-stage ventricular therapy having at least two and not more thanten ventricular pulses of at least 2 volts and not more than 100 voltsfor unpinning of one or more singularities associated with a ventriculararrhythmia; a second stage of the three-stage ventricular cardioversiontherapy having at least six and not more than ten far field pulses ofless than a ventricular far-field excitation threshold with a pulsecoupling interval of 70-100% of the cycle length of the ventriculararrhythmia for anti-repinning of the one or more singularitiesassociated with the ventricular arrhythmia; and a third stage of thethree-stage cardioversion therapy having at least eight and not morethan twelve near field pulses at a voltage substantially ranging fromtwo to four times the diastolic pacing threshold with a pulse couplinginterval of between 70-100% of the cycle length of the ventriculararrhythmia for extinguishing of the one or more singularities associatedwith the ventricular arrhythmia, and wherein the three-stage ventriculartherapy is delivered in response to detection of the ventriculararrhythmia with each stage having an inter-stage delay of between 50 to800 milliseconds.